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Integrative Therapies for Depression - Serotonin Precursors - 5-hydorxytryptophan (5-HTP)

Scott Olson, ND

5-hydorxytryptophan (5-HTP) is a compound made from the amino acid (protein) tryptophan and is primarily found in the brain. 5-HTP is one of the basic building blocks for serotonin, a neurotransmitter (brain chemical) thought to be responsible for mood regulation. Individuals who experience depression and anxiety have reduced levels of serotonin in their brains.

Antidepressant medications such as the selective serotonin reuptake inhibitors (SSRI) and monoamine oxidase inhibitors (MAOI) are commonly used to treat depression. These medications work by increasing the total amount of serotonin in the brain or by allowing the serotonin that is already there to work longer.

Serotonin itself can be manufactured in the laboratory, but when taken as a supplement, it cannot reach the brain (it does not have the ability to cross from general blood circulation into brain circulation, because of a selective membrane that only allows certain chemicals into the brain). Multiple research studies support the use of 5-HTP as a natural way to increase brain serotonin levels. Some research has also supported the use of 5-HTP for treating depression, but the studies are based on small groups of people, limiting the conclusions that can be drawn about the potential benefits of 5-HTP for all types of depressed individuals.

Safety and Dosing

A typical dose of 5-HTP is between 150-300 mg a day. 5-HTP must not be used with any other antidepressant medication because of the risk of a rare condition called serotonin syndrome (or serotonin toxicity) that produces mental confusion, agitation, headache, shivering, sweating, hypertension (high blood pressure), tachycardia (fast heart rate), and other symptoms. 5-HTP also may interfere with lithium (a medication typically used for bipolar disorder).

Side Effects of 5-HTP

  • Agitation
  • Drowsiness
  • Flushing
  • Headache
  • Mild stomach upset
  • Tachycardia (fast heart rate)

There is a small risk of developing liver toxicity when using 5-HTP. L-tryptophan, a closely related chemical, was pulled from shelves in 1989 when it was associated with liver failure in a few people taking the supplement. While it appears that 5-HTP does not cause this problem, it is best to check with your health practitioner before starting any new medication, especially if you currently have (or have a history of) liver problems.

WARNING: Any substance that increases serotonin carries with it the risk of causing a manic episode in people with bipolar disorder (manic depression). A manic episode, the high energy component of bipolar disorder, is characterized by a euphoric (joyful, energetic) mood, hyperactivity, a positive and expansive or agitated outlook on life, a hyper-inflated inflated sense of self-esteem, impulsive and risky behavior, and a reduced need for sleep. While the use of 5-HTP hasn't been linked to manic episodes, caution is still warranted. Consult your health care provider before taking 5-HTP if you have bipolar disorder.


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